红细胞同种抗-E抗体对输血不良事件和新生儿溶血病的影响及形成机制研究

发布时间：2018-04-30 13:05

本文选题：红细胞同种抗体 + 迟发型溶血性输血反应　；参考：《武汉大学》2014年博士论文

【摘要】：红细胞同种抗体是引起临床输血不良事件及新生儿溶血病的直接原因,来源于献血者或胎儿的外源性红细胞抗原可刺激机体免疫系统,使其产生针对外源性红细胞抗原的同种抗体,而红细胞同种抗-E抗体是临床上最常见的抗体。临床对红细胞同种抗体导致的输血不良事件及新生儿溶血病往往在发生后才进行治疗,且易引起误诊或被忽略,影响了患者的临床治疗,甚至导致严重的后果。在临床输血实践中,为预防此类事件的发生,国内外仅有少数机构对已产生红细胞同种抗体的受血者进行特异性抗原匹配输血,但因为这种技术费力、费时、增加患者经剂负担且需要专业人才进行操作,影响了其普及性；而对预防红细胞同种抗-E抗体引起的新生儿溶血病目前尚无有效方法。针对上述不足,本研究旨在探讨红细胞同种抗-E抗体的形成机制,为临床积极有效预防和治疗该抗体引起的临床输血不良事件及新生儿溶血病提供科学依据。第一部分红细胞同种抗-E抗体引起输血不良反应及新生儿溶血病的风险及作用机制研究目的：通过调查汉族住院人群红细胞同种抗体特异性、风险及流行情况,探讨红细胞同种抗-E抗体引起输血不良反应及新生儿溶血病的风险及机制。研究方法：利用微柱凝集技术对42517例汉族住院患者进行了红细胞同种抗体筛选。对抗体筛选阳性的患者标本再用经典试管法进行红细胞同种抗体特异性鉴定。同时收集抗体筛选阳性患者的临床资料,如性别、年龄、输血史、妊娠史、红细胞同种抗体检测记录、输血反应及新生儿溶血病记录等以分析抗体的发生率、特异性、风险及作用机制。研究结果：本研究在42517例住院患者中共检测出212例带有红细胞同种抗体,红细胞同种抗体总的发生率为0.50%,且在不同性别和年龄之间其发生率显著不同。检出抗体最多的依次为抗-E(87/212,41.0%)、抗-D(45/212,21.2%)、抗-M(41/212,19.3%)和抗-cE(13/212,6.1%)。在212例带有红细胞同种抗体患者中,共发现有17例婴儿发生新生儿溶血病,其中13例由抗-D引起、3例由抗-E引起、1例由抗-Fya引起；另有4例患者在输血后发生了迟发型溶血性输血反应。研究结论：在汉族住院人群中,红细胞同种抗体总的发生率为0.50%,其中抗-E、抗-D和抗-M是最常见的抗体。抗-D和抗-E是引起新生儿溶血病或迟发型溶血性输血反应的主要风险因素。第二部分红细胞E抗原对E抗体产生的影响及风险评估研究目的：由于红细胞同种抗-E抗体是最常见的有临床意义的抗体,因此本研究主要探讨外源红细胞E抗原对红细胞制品输注患者同种抗-E抗体形成的影响及风险。研究方法：检测1239例接受红细胞制品输注患者及1306例供血者红细胞E抗原,并从1239例接受红细胞制品输注的患者中筛选出258例具有接受外源红细胞E抗原刺激风险人群,监测这些筛选人群在住院期间接受外源红细胞E抗原刺激后的红细胞同种抗-E抗体产生情况。研究结果：在随机选取的接受红细胞制品输注人群中,约1/4的人群有接受外源红细胞E抗原刺激的风险。在筛选出具有接受外源红细胞E抗原刺激风险人群中,尽管约半数曾经有输血史和/或妊娠史,甚至其中30例曾经有过多次输血史和/或妊娠史,且其中12例在本次研究中又接受过多次外源红细胞E抗原刺激,但本研究在这些人群中并未检出红细胞同种抗-E抗体或其他类红细胞同种抗体。研究结论：接受红细胞制品输注人群具有较高接受外源红细胞E抗原刺激的风险,并且是启动红细胞同种抗-E抗体形成的机制之一,但不一定会产生红细胞同种抗-E抗体。第三部分免疫调节基因TRIM21对红细胞同种抗-E抗体产生的影响及机理分析研究目的：通过分析红细胞同种抗-E抗体产生患者不同性别、不同年龄间免疫调节基因TRIM21rs660位点变异情况及不同等位基因间细胞和体液免疫功能,探讨该变异对红细胞同种抗-E抗体产生的影响及机理。研究方法：通过基因测序的方法,检测49例红细胞同种抗-E抗体产生患者和35例未产生红细胞同种抗-E抗体对照者TRIM21基因rs660位点变异情况,分析其等位基因在不同性别、不同年龄组间的分布情况,同时检测了20例患者组和15例对照组人群不同等位基因间的细胞和体液免疫功能,并进行比较分析,以探讨其对红细胞同种抗-E抗体产生的影响及机理。研究结果：在产生红细胞同种抗-E抗体患者组中,携带有T等位基因的患者共有31例,携带有C等位基因的患者共有18例,TRIM21基因rs660位点不同等位基因在产生红细胞同种抗-E抗体患者组不同性别之间分布差异无显著性(P0.05)。在未产生红细胞同种抗-E抗体对照组中,携带有T等位基因的患者共有26例,携带有C等位基因的患者共有9例,TRIM21基因rs660位点不同等位基因在未产生红细胞同种抗-E抗体对照组不同性别之间分布差异无显著性(P0.05)。在患者组和对照组之间,TRIM21基因rs660位点不同等位基因分布差异无显著性(P0.05),而在不同性别间,TRIM21基因rs660位点不同等位基因的分布差异亦无显著性(P0.05)。在5岁年龄组中,T等位基因的患者共有9例,C等位基因的患者共有5例；5-10岁年龄组中,T等位基因的患者共有11例,C等位基因的患者共有5例；10岁年龄组中,T等位基因的患者共有13例,C等位基因的患者共有6例。经对不同年龄组间TRIM21基因rs660位点不同等位基因的分布比较发现,其在不同年龄组间的分布差异均无显著性(P0.05)。在患者组和对照组TRIM21基因rs660不同等位基因间,细胞和体液免疫功能差异均无显著性(P0.05)。研究结论：在产生红细胞同种抗-E抗体的患者人群和未产生红细胞同种抗-E抗体的对照组人群,TRIM21基因rs660位点T等位基因频率均高于C等位基因频率。在不同的性别和年龄之间,TRIM2基因rs660位点等位基因的分布差异不存在显著性。在TRIM21基因rs660不同等位基因间,研究人群细胞和体液免疫功能并无显著性变化。本研究人群中,TRIN(?)21基因rs660位点变异不影响红细胞同种抗-E抗体的产生。
[Abstract]:Erythrocyte homoantibody is the direct cause of the adverse events of clinical transfusion and hemolytic disease of the newborn. The exogenous erythrocyte antigen derived from the donor or fetus can stimulate the immune system and produce the homologous antibody against the exogenous erythrocyte antigen, and the erythrocyte homoisoanti -E antibody is the most common antibody in the clinic.
The adverse events of blood transfusion caused by erythrocyte homoisoantibody and the hemolytic disease of the newborn are often treated, and it is easy to cause misdiagnosis or neglect, which affects the clinical treatment of the patients and even causes serious consequences. In the practice of clinical transfusion, only a few institutions have produced to prevent this kind of thing from happening at home and abroad. The blood recipients of the erythrocyte homoantibody match the blood of the specific antigen to match the blood transfusion, but because this technique is difficult and time-consuming, it will increase the burden of the patient and need professional operation, which affects its popularity, and there is no effective method for preventing the hemolytic disease of the newborn caused by the erythrocyte homoisoanti -E antibody. The aim of this study is to explore the formation mechanism of erythrocyte isoanti -E antibody, and provide a scientific basis for the clinical active effective prevention and treatment of the adverse clinical transfusion events caused by the antibody and the hemolytic disease of the newborn.
Part one the risk and mechanism of transfusion induced adverse reactions and hemolytic disease of the newborn caused by -E antibody against red blood cells
The purpose of the study is:
By investigating the specificity, risk and prevalence of erythrocyte homograft antibodies in the Han population in the Han population, the risk and mechanism of erythrocyte allogeneic anti -E antibody caused by blood transfusion and hemolytic disease of the newborn were investigated.
Research methods:
Using the microcolumn agglutination technique, 42517 cases of Han hospitalized patients were screened for erythrocyte homograft antibody. The specific identification of erythrocyte homograft antibody was carried out by the classical test tube method. The clinical data of antibody screening positive patients, such as sex, age, blood transfusion history, pregnancy history, erythrocyte homohomoisoresistance, were collected. The incidence, specificity, risk and mechanism of antibody were analyzed by physical examination, blood transfusion reaction and neonatal hemolytic disease.
The results of the study:
In this study, 212 cases of erythrocyte homohomoantibody were detected in 42517 hospitalized patients. The total incidence of erythrocyte homoantibody was 0.50%, and the incidence of the antibody was significantly different between different sex and age. The highest detection antibodies were anti -E (87/212,41.0%), anti -D (45/ 212,21.2%), anti -M (41/212,19.3%) and -cE (13/212,6.1%). In 212 patients with erythrocyte homograft antibody, 17 cases of neonatal hemolytic disease were found, of which 13 were caused by anti -D, 3 were caused by anti -E, 1 were caused by anti -Fya, and 4 patients had delayed hemolytic transfusion after blood transfusion.
The conclusions are as follows:
In the Han population, the total incidence of erythrocyte homoisoantibodies is 0.50%, of which anti -E, anti -D and anti -M are the most common antibodies. Anti -D and anti -E are the main risk factors for neonatal hemolytic disease or delayed hemolytic transfusion reaction.
The second part is the influence of erythrocyte E antigen on the production of E antibody and its risk assessment.
The purpose of the study is:
Because erythrocyte isoanti -E antibody is the most common clinical antibody, this study mainly discusses the effect and risk of exogenous E antigen on the formation of allogeneic anti -E antibody in erythrocyte infusion patients.
Research methods:
The erythrocyte E antigen was detected in 1239 cases of erythrocyte infusion and 1306 cases of blood donors, and from 1239 patients receiving erythrocyte infusion, 258 patients with the risk of exogenous erythrocyte E antigen stimulation were screened, and these screening people were monitored to receive erythrocyte homohomoisoresistance after the external erythrocyte E antigen stimulation during hospitalization. The production of -E antibody.
The results of the study:
Among the randomly selected recipients of the transfusion of red cell products, about 1/4 of the population had a risk of receiving E antigen stimulation of the exogenous erythrocyte. Among the people who had been screened for the risk of E antigen stimulation with exogenous erythrocytes, about half of them had a history of blood transfusion and / or pregnancy history, and even 30 of them had had a history of multiple blood transfusions and / or pregnancy history, and In this study, 12 of the 12 cases received a number of exogenous erythrocyte antigen stimuli, but this study did not detect erythrocyte isoanti -E antibodies or other erythrocyte homograft antibodies.
The conclusions are as follows:
The population receiving erythrocyte infusion has a high risk of receiving the stimulation of the E antigen of the foreign red cell, and is one of the mechanisms to initiate the formation of the anti -E antibody of the red blood cell, but it does not necessarily produce the erythrocyte isoanti -E antibody.
The third part is the effect of immunomodulatory gene TRIM21 on the production of red blood cell homologous anti -E antibody and its mechanism.
The purpose of the study is:
The effect and mechanism of the mutation on the production of erythrocyte isoanti -E antibody were investigated by analyzing the variation of TRIM21rs660 loci in different ages and the cell and humoral immune function between different alleles by analyzing the sex of the erythrocyte isoanti -E antibody in different sex, the variation of the immunomodulatory gene in different ages and the immune function of different alleles.
Research methods:
The mutation of TRIM21 gene locus in 49 cases of erythrocyte isoanti -E antibody production and 35 cases of non erythrocyte isoanti -E antibody control was detected by gene sequencing, and the distribution of alleles in different sex and age groups was analyzed, and 20 patients and 15 control groups were detected at the same time. The cellular and humoral immune functions between the alleles were compared and analyzed to explore the effect and mechanism of its -E antibody production.
The results of the study:
There were 31 patients with T allele and 18 patients carrying C allele in the patients with erythrocyte allogeneic anti -E antibody. There was no significant difference between the different sex alleles of the TRIM21 gene rs660 loci in the group that produced the erythrocyte isoanti -E antibody group (P0.05). No red cell homohomoisoresistance was produced. In the -E antibody control group, there were 26 patients with T allele and 9 patients with C allele, and there was no significant difference in the distribution of TRIM21 gene rs660 alleles between different sex alleles of the erythrocyte allogeneic anti -E antibody control group (P0.05). The rs660 locus of TRIM21 gene between the patient group and the control group was between the patient group and the control group. There was no significant difference in the distribution of alleles in different alleles (P0.05), but there was no significant difference in the distribution of alleles at the rs660 locus of the TRIM21 gene in the same sex (P0.05).
In the age group of 5, there were 9 patients with T allele and 5 patients with C allele; 11 patients with T allele in 5-10 year old age group and 5 patients with C allele; 10 age group, T allele were 13, and C alleles were 6. The TRIM21 gene R between different age groups The distribution of alleles at s660 locus showed no significant difference among different age groups (P0.05).
There was no significant difference in cellular and humoral immune function between TRIM21 and rs660 alleles in patients and controls (P0.05).
The conclusions are as follows:
The frequency of the T allele of the TRIM21 gene rs660 loci was higher than the C allele frequency in the population of the patients who produced the erythrocyte homograft anti -E antibody and the anti -E antibody of the erythrocytes. The distribution difference of the TRIM2 gene rs660 loci allele was not significant between the different sex and age. The TRIM21 gene rs66 was not significant. The TRIM21 gene rs66 was not significant. There was no significant change in cell and humoral immune function between the 0 different alleles. The rs660 locus mutation of the TRIN (?) 21 gene did not affect the production of erythrocyte isoanti -E antibody in this study population.

【学位授予单位】：武汉大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R722.18;R457.1

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